Attenuation by electroconvulsive shock and antidepressant drugs of the 5-HT1A receptor-mediated hypothermia and serotonin syndrome produced by 8-OH-DPAT in the rat

Abstract

The hypothermia and motor behavioural syndrome produced in rats by injection of the 5-HT_1A ligand 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been studied following administration of electroconvulsive shock under halothane anaesthesia (ECS) and during the administration of antidepressant drugs. Repeated ECS attenuated the hypothermic response to 8-OH-DPAT (0.1 mg/kg SC) immediately after the last of five shocks given spread out over 10 days with a maximal effect 21 days after the final shock. A single ECS was without effect. The serotonin syndrome produced by 8-OH-DPAT (0.75 mg/kg SC) was also attenuated, although simple motility was increased. Zimeldine (20 mg/kg) and desipramine (20 mg/kg), when given once daily for 14 days also attenuated the hypothermia and the serotonin syndrome provoked by 8-OH-DPAT. The hypothermic response was somewhat reduced 24 h after a single injection of zimeldine but not 45 min after zimeldine (5 mg/kg IP). At a high dose (20 mg/kg) tranylcypromine clearly attenuated both responses 24 h after a single injection. Tranylcypromine (6 mg/kg IP) showed a smaller effect after a single injection but attenuated the behavioural syndrome on repeated administration. Repeated injection of flurazepam (10 mg/kg IP) was without effect on either the behavioural or hypothermic response to 8-OH-DPAT. These findings are consistent with the view that responses mediated via the 5-HT_1A receptor may be involved in the mechanism of action of antidepressant treatments.